Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Elevated intraspinal pressure in traumatic spinal cord injury is a promising therapeutic target.

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.

Implant complications after one-level or two-level cervical disc arthroplasty: A retrospective single-centre study of 105 patients.

The aim of study was to investigate the complications of cervical disc arthroplasty (CDA) and to discuss the factors affecting the mobility of the prosthesis and the measures to prevent these complications. Hundred and five patients who underwent CDA between 2009 and 2016 were enrolled. The clinical and radiographic outcomes were used to assess and the complications were recorded as well.All the patients were followed-up with an average of 41.30 ±â€Š16.90 months with an average age of 47.90 ±â€Š9.22 years. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores improved significantly at the final follow-up (FU) compared with the preoperative values. At the final FU, the overall incidence of heterotopic ossification (HO) was 51.42%. The distribution of different grades of HO was low-level HO (53.7%) and high-level HO (46.3%). No significant differences were found in the NDI, VAS, or JOA scores between patients with HO and those without HO (P > .05). In the high-level HO patients, the range of mobility (ROM) was significantly reduced compared with the low-level HO patients and those without HO (P < .05). The anterior displacement, subsidence, and instability were observed in 1 patient respectively and the segmental kyphosis, adjacent segment degeneration in 3 patients respectively. The patient of CDA instability also suffered severe neck pain and the revision surgery was performed.Postoperative complications in CDA such as HO, segmental kyphosis, and prosthesis displacement are prone to occur, affecting prosthesis mobility. Surgical indications should be strictly controlled, and intraoperative and postoperative treatments should be given great attention in order to reduce prosthesis-related complications.

EMT-related gene expression is positively correlated with immunity and may be derived from stromal cells in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of bone cancer in children and young adults. Recent studies have shown a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and immunity in human cancers. Here, we investigated the relationship among EMT, immune activity, stromal activity and tumor purity in osteosarcoma. METHODS: We defined EMT gene signatures and evaluated immune activity and stromal activity based on the gene expression and clinical data from three independent microarray datasets. These factors were evaluated by single sample Gene Set Enrichment Analyses and the ESTIMATE tool. Finally, we analyzed the key source of EMT gene expression in osteosarcoma using microarray datasets from the Gene Expression Omnibus and human samples that we collected. RESULTS: EMT-related gene expression was positively correlated with immune and stromal activity in osteosarcoma. Tumor purity was negatively correlated with EMT, immune activity and stromal cells. We further demonstrated that high EMT gene expression could significantly predict poor overall survival (OS) and recurrence-free survival (RFS) in osteosarcoma patients, while high immune activity cannot. However, combining these factors could have further prognostic value for osteosarcoma patients in terms of OS and RFS. Finally, we found that stromal cells may serve as a key source of EMT gene expression in osteosarcoma. CONCLUSION: The results of this study reveal that the expression of EMT genes and immunity are positively correlated, but these signatures convey disparate prognostic information. Furthermore, the results indicate that EMT-related gene expression may be derived from stromal rather than epithelial cancer cells.

High expression of ID1 facilitates metastasis in human osteosarcoma by regulating the sensitivity of anoikis via PI3K/AKT depended suppression of the intrinsic apoptotic signaling pathway.

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma.

Mid-term efficacy and safety of cervical disc arthroplasty versus fusion in cervical spondylosis: A systematic review and meta-analysis.

Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are the most commonly used procedures in cervical spondylosis. However, only a few published studies exist in the literature comparing these two operation types, particularly its mid-term efficacy and safety. Furthermore, in those studies, even large sample trials, when compared, have elicited controversial results, making it inconvenient for clinicians to refer to them. The aim of the present study was to clarify the advantages and shortcomings of the two procedures. Articles indexed in the PubMed, Web of Science, Cochrane Library, EMBASE, China Biological Medicine and China National Knowledge Infrastructure (CNKI) databases, as of March 2016, that met our criteria were searched. A total of 18 trials involving 3,040 patients were included in our final analysis. The most important results drawn from the present analysis were as follows: Insignificant differences were identified in the blood loss [weighted mean difference (WMD)=6.23; 95% confidence intervals (CI), -0.85 to 13.32; P=0.08], surgical time [standardized mean difference (SMD)=0.40; 95% CI, -0.01 to 0.82; P=0.06], the time of hospital stay (SMD=0.05; 95% CI, -0.28 to 0.37; P=0.77) and the total complications rate [odds ratio (OR)=0.86; 95% CI, 0.66 to 1.131; P=0.28] on a comparison of the two operation methods. By contrast, comparing CDA with ACDF, the CDA had higher Short Form survey (SF-36) scores (WMD=1.65; 95% CI, 0.61 to 2.69; P=0.002), a larger range of motion in the operation level (SMD=6.53; 95% CI, 3.89 to 9.17; P<0.0001), a higher rate of neurological improvement following the operation (OR=1.80; 95% CI, 1.29 to 2.52; P=0.0006), a lower Visual Analog Scale (VAS) score of neck pain (WMD= 0.16; 95% CI, -0.28 to 0.05; P=0.006) and arm pain (WMD= 0.12; 95% CI, -0.24 to -0.01; P=0.04). In addition, in the mid-term following the surgery, CDA had a lower Neck Disability Index (NDI; SMD=0.18; 95% CI, -0.28 to -0.07; P=0.001) and a lower reoperation rate of adjacent levels (OR=0.54; 95% CI, 0.35 to 0.85; P=0.007) compared with ACDF. Taken together, these results suggested that CDA and ACDF are efficient and safe methods for dealing with cervical spondylosis. However, with respect to certain specific indicators, such as the reoperation rate of adjacent levels following surgery, the former has several advantages.

MicroRNA-212 inhibits osteosarcoma cells proliferation and invasion by down-regulation of Sox4.

BACKGROUND: Multiple MicroRNAs (miRNAs) have been identified in the development and progression of osteosarcoma. However, the expression and roles of miR-212 in osteosarcoma remain largely undefined. METHODS: Real-time PCR assays were used to detect the expression of miR-212 in human osteosarcoma tissues. MiR-212 mimics were introduced into MG63 and U2OS cells. Bioinformatic prediction was used to identify the potential targets of miR-212. Protein expression analysis, luciferase assays and rescue assays were used to confirm the substrate of miR-212. RESULTS: miR-212 was significantly down-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. Introduction of miR-212 mimics into MG63 and U2OS cells inhibited cell proliferation and invasion. Besides, miR-212 overexpression could also inhibit tumor growth in the nude mice. Additionally, bioinformatic prediction suggested that the sex-determining region Y-box 4 (Sox4) is a target gene of miR-212. Sox4 inhibition phenocopied the roles of miR-212, while restored expression of Sox4 dampened miR-212-mediated suppression of tumor progression. CONCLUSION: The miR-212/Sox4 interaction plays an important role of in the osteosarcoma progression.

The effects of NSAIDs on types I, II, and III collagen metabolism in a rat osteoarthritis model.

The effects of long-term use of celecoxib, ibuprofen, and indomethacin on types I, II, and III collagen metabolism were evaluated in rat osteoarthritis (OA) model. One hundred and thirty wistar rats were randomly divided into 4 groups: the celecoxib group, the ibuprofen group, the indomethacin group, and the normal saline group. The osteoarthritis was induced by the excision of the left Achilles tendon. In the 3rd, 6th, and 9th month of treatment after surgically induced osteoarthritis, the articular cartilage was observed with microscope using HE staining. The expression of proteoglycans was semiquantified using toluidine blue staining. And, the expressions of types I, II, and III collagen in chondrocytes were examined using immunohistochemistry. The results suggested that celecoxib had no remarkable effects on the expression of types I, II, and III collagen. Ibuprofen upgraded the expression of types I, II, and III collagen and increased the synthesis of collagen. Indomethacin suppressed the expression of type II collagen and enhanced the expression of types I and III collagen. Therefore, during the long-term use of NSAIDs in osteoarthritis, celecoxib may have no remarkable influences on collagen metabolism of the articular cartilage and may be the ideal choice in the treatment of chronic destructive joint disease when anti-inflammatory drugs need to be used for a prolonged period. Ibuprofen may be unfavorable, and indomethacin may be harmful to collagen metabolism in OA treatment.

[Biomechanical evaluation of three-dimensional stability of anterior approach screw fixation through C2 vertebral body to C1 lateral mass].

OBJECTIVE: To determine the three-dimensional stability of C1-C2 after anterior approach screw fixation through C2 vertebral body to C1 lateral mass for C1-C2 instability or dislocation. METHODS: The three-dimensional range of motion of atlantoaxial joint were measured in 16 human cadaveric specimens under four conditions: the intact state (1st group), odontoid fracture of type II (2nd group), instrumentation with posterior C1-C2 trans-articular screw fixation (Magerl technique) (3rd group) and anterior approach screw fixation through C2 vertebral body to C1 lateral mass (4th group) respectively. RESULTS: There was generally significant difference between 1st group and other groups and between 2nd group and other groups by statistics analysis (P < 0.001). Range of motion significantly decreased in 3rd group and 4th group in all directions. There was generally no significant difference between the two methods by statistical analysis (P > 0.05). CONCLUSION: Anterior approach screw fixation through C2 vertebral body to C lateral mass provides satisfied stability. It provides the equivalent effect to Magerl technique. It is a kind of reliable surgery choice for the treatment of instability or dislocation of C1-C2 joint.